About

Thomas F. Gajewski is a Professor at the University of Chicago in the Department of Pathology. His research activities focus on immunotherapy and tumor microenvironment, with a particular emphasis on overcoming resistance to immune checkpoint inhibitors such as anti-PD1 therapy. His work involves studying the molecular and cellular mechanisms underlying anti-tumor immunity, including the roles of T cells, myeloid cells, and dendritic cells in cancer progression and treatment response. Gajewski's contributions include investigating the genetic and biochemical factors that influence immune responses in melanoma and other solid tumors. His research aims to enhance the efficacy of immunotherapies by understanding immune resistance mechanisms and developing strategies to modulate the tumor microenvironment. He has been involved in numerous NIH-funded projects as a Principal Investigator, exploring pathways such as STING, T cell regulation, and immune tolerance, and their implications for cancer therapy.

Research topics

• Medicine
• Internal medicine
• Oncology
• Cancer research
• Biology
• Gastroenterology
• Immunology
• Genetics
• Pathology
• Bioinformatics
• Surgery

Selected publications

• Supplementary figure S6 from Tumor Cell–Intrinsic <i>Decr2</i> Regulates Ferroptosis and Immunotherapy Efficacy

  2025-08-01

  preprintOpen accessSenior author

  <p>Supplementary Figure S6. Gating strategy for Flow cytometry analysis of B16.SIY tumor microenvironment isolated from B6 mice.</p>

  PublisherOA PDFDOI

• Supplementary Figure 5 from PKCδ Germline Variants and Genetic Deletion in Mice Augment Antitumor Immunity through Regulation of Myeloid Cells

  2025-04-02

  preprintOpen accessSenior author

  <p>GSEA reveals many macrophage-related gene sets that are enriched in the C1qa DEG list.</p>

  PublisherDOI

• Supplementary figure S16 from Tumor Cell–Intrinsic <i>Decr2</i> Regulates Ferroptosis and Immunotherapy Efficacy

  2025-08-01

  preprintOpen accessSenior author

  <p>Supplementary Figure S16. IFN-γ signaling is involved with T cell killing and reprogrammed lipids</p>

  PublisherOA PDFDOI

• Supplementary figure S11 from Tumor Cell–Intrinsic <i>Decr2</i> Regulates Ferroptosis and Immunotherapy Efficacy

  2025-08-01

  preprintOpen accessSenior author

  <p>Supplementary Figure S11. Decr2 knockdown tumors are resistant to ferroptosis.</p>

  PublisherOA PDFDOI

• Supplementary figure S12 from Tumor Cell–Intrinsic <i>Decr2</i> Regulates Ferroptosis and Immunotherapy Efficacy

  2025-08-01

  preprintOpen accessSenior author

  <p>Supplementary Figure S12. The gating strategy for flow cytometry analysis of lipid reactive oxygen species (ROS).</p>

  PublisherOA PDFDOI

• Supplementary figure S3 from Tumor Cell–Intrinsic <i>Decr2</i> Regulates Ferroptosis and Immunotherapy Efficacy

  2025-08-01

  preprintOpen accessSenior author

  <p>Supplementary Figure S3. Decr2 modulates tumor sensitivity to anti-PD-L1 therapy in vivo.</p>

  PublisherOA PDFDOI

• Supplementary figure S2 from Tumor Cell–Intrinsic <i>Decr2</i> Regulates Ferroptosis and Immunotherapy Efficacy

  2025-08-01

  preprintOpen accessSenior author

  <p>Supplementary Figure S2. Decr2 knockdown OCI-Ly8 tumor cells were resistant to CD19-CAR T cell killing in vitro and Decr2 knockdown B16.SIY tumors exhibit resistance to anti-PD-L1 therapy in vivo.</p>

  PublisherOA PDFDOI

• Supplementary figure S8 from Tumor Cell–Intrinsic <i>Decr2</i> Regulates Ferroptosis and Immunotherapy Efficacy

  2025-08-01

  preprintOpen accessSenior author

  <p>Supplementary Figure S8. Gating strategy for Flow cytometry analysis of B16.SIY tumor microenvironment isolated from B6 mice.</p>

  PublisherOA PDFDOI

• Data from PKCδ Germline Variants and Genetic Deletion in Mice Augment Antitumor Immunity through Regulation of Myeloid Cells

  2025-04-02

  preprintOpen accessSenior author

  <div>Abstract<p>Based on the notion that hypomorphic germline genetic variants are linked to autoimmune diseases, we reasoned that novel targets for cancer immunotherapy might be identified through germline variants associated with greater T-cell infiltration into tumors. Here, we report that while investigating germline polymorphisms associated with a tumor immune gene signature, we identified protein kinase C delta (PKCδ) as a candidate. Genetic deletion of <i>Prkcd</i> in mice resulted in improved endogenous antitumor immunity and increased efficacy of anti–PD-L1. Single-cell RNA sequencing revealed myeloid cell expression of <i>Prkcd</i>, and PKCδ deletion caused a shift in macrophage gene expression from an M2-like to an M1-like phenotype. Conditional deletion of <i>Prkcd</i> in myeloid cells recapitulated improved tumor control that was augmented further with anti–PD-L1. Analysis of clinical samples confirmed an association between <i>PRKCD</i> variants and M1/M2 phenotype, as well as between a PKCδ knockout–like gene signature and clinical benefit from anti–PD-1. Our results identify PKCδ as a candidate therapeutic target that modulates myeloid cell states.</p></div>

  PublisherDOI

• Data from Tumor Cell–Intrinsic <i>Decr2</i> Regulates Ferroptosis and Immunotherapy Efficacy

  2025-08-01

  preprintOpen accessSenior author

  <div>Abstract<p>Immune checkpoint blockade therapies have transformed the landscape of cancer care, but durable clinical responses are achieved in only a subset of patients. To identify genes that can contribute to immunotherapy resistance, a genome-wide CRISPR screen was performed. Selection for mutants that are resistant to T cell–mediated killing identified the gene encoding <i>Decr2</i>, a peroxisomal 2,4-dienoyl-CoA reductase. We show that <i>Decr2</i> in tumor cells participates in CD8<sup>+</sup> T cell–mediated tumor cell killing and that <i>Decr2</i> knockdown reduces the efficacy of anti–PD-L1 therapy <i>in vivo</i>. Knocking down <i>Decr2</i> expression resulted in diminished ferroptosis that was associated with reduced induction of polyunsaturated ether phospholipids. Analysis of tumor RNA sequencing data from patients with melanoma revealed that upregulation of <i>Decr2</i> was associated with anti–PD-1 efficacy, and patients with <i>Decr2</i> gene deletions showed worse clinical outcomes. Our results identify <i>Decr2</i> as a regulator of immunomediated tumor cell killing, with implications for improving immunotherapy efficacy.</p></div>

  PublisherDOI

Recent grants

• NIH Grant R01AI047919

  NIH · $1.4M · 2006

• NIH Grant R21AI053886

  NIH · $295k · 2004

• NIH Grant P01CA097296

  NIH · $12.5M · 2014

• NIH Grant R01AI080745

  NIH · $780k · 2011

• NIH Grant R01CA198496

  NIH · $433k · 2016

Frequent coauthors

• Jason J. Luke

  336 shared

• Yuanyuan Zha

  Second Military Medical University

  306 shared

• Theodore Karrison

  University of Chicago

  254 shared

• Gini F. Fleming

  248 shared

• Mark J. Ratain

  University of Chicago

  248 shared

• Linda Janisch

  235 shared

• Ralph R. Weichselbaum

  University of Chicago

  234 shared

• Steven J. Chmura

  University of Chicago

  234 shared